This research has three objectives: (1) cultivation of M. leprae in tissue culture; (2) investigation of various methods for immunosuppressing rats to obtain a long-term uniform infection yielding large numbers of M. leprae for the tissue culture studies; and (3) the utilization of immunosuppressed rats as animal models for the study of leprosy, with reference to their use in evaluation of chemotherapeutic agents. We have been able to show that neonatally thymectomized rats inoculated intravenously with M. leprae develop a disseminated infection in all of the cooler sites of the body within a year after infection. These heavily infected tissues will be cultivated in vitro with the expectation that M. laprae will continue to replicate in he same cells that were parasitized in vivo. We will also determine the optimum amount of additional immunosuppression in the form of sublethal X-irradiation that can be administered to thymectomized rats to enhance intravenous M. leprae infection further. We will also use these animals as models of human lepromatous leprosy in the evaluation of potentially eradicative chemotherapeutic regimens. Attempts will also be made to demonstrate that because the thymectomized rat is more highly susceptible to M. leprae infection than the currently used intact mouse, it may be the animal of choice in testing human tissues for residual viable organisms after a course of chemotherapy.